This proving is reprinted here on provings.info website with the kind permission of Steve Smith, principal of the South Downs School of Homeopathy. Please visit the schools website for further information: www.homoeopathyschool.com For further information on homeopathy please see Steve Smiths book: Medical Homoeopathy ISBN (13) 9781874581901 medhom@winterpress.net

SOUTH DOWNS SCHOOL OF HOMEOPATHY

PROVING OF ASPARTAME

July 2003

Richard Bocock 67a St Peters Street

Islington London N1 8JR

Tel: 020 7226 8705 e-mail: richjb@blueyonder.co.uk

BACKGROUND This proving was carried out by students at the South Downs School of Homeopathy between January and April 2002. My thanks to the students for their commitment to the proving and diligence in carrying out their roles as provers and supervisors, in what was a very challenging and long last proving. My thanks also to Christian Taylor who did most of the work of writing up this proving, and Gill Bowden who did the research on the remedy substance. WHY THIS PROVING? I read a spate of articles in the press and on the Internet about the possible side effects of using this artificial sweetener in our diet obsessed world. Its use is very widespread in diet drinks and foods and I was curious to see first of all if the homeopathic proving mirrored the reported side effects of the material substance, and wondered if there might indeed be an Aspartame constitution or layer engrafted on those who ingested a lot of the substance either directly, or indirectly in the womb. THE REMEDY The remedy was made up by Helios Pharmacy. It is an entirely new remedy. THE PROVERS The proving was started in January 2002. It was conducted using the guidelines contained in The Dynamics and Methodology of Homeopathic Provings by Jeremy Sherr. The provers were instructed to take up to a maximum of three doses, twice a day, for a maximum of two days and to stop as soon as symptoms appeared. There were seven provers: Prover Gender Potency Comments 1 Female 6c 2 Female Placebo No symptoms reported 3 Female 30c 4 Female 12c 5 Female 12c 6 Female 30c 7 Female 6c Provers, supervisors and the proving coordinator did not know what potency they were being given. One dose of placebo was also included, and interestingly this proved reported next to no symptoms.

LAYOUT OF PROVING The following text includes information on the substance itself and the proving symptoms grouped according to key themes using the provers own language. No attempt is made to integrate this pure information or to suggest a material medica picture. A fuller synthesis suggesting a material medica picture is written separately and will be published in appropriate journals. Toxicological data on Aspartame has not been included at this stage in the repertorisation although it might be beneficial to add this in to expand the picture and suggest additional rubrics if time permits at a later stage. However due to the controversial and anecdotal nature of some of this information it could prove difficult to know what to include and what to exclude. REPERTORISATION All rubrics are from the Complete Repertory. FEEDBACK Please forward any more information, clinical experience or comments to Richard Bocock at richjb@blueyonder.co.uk RICHARD BOCOCK PROVING COORDINATOR

ASPARTAME L-aspartyl-L-phenylalanyl methyl ester, also known as aspartame, NutraSweet, Equal, Candarel, Spoonful and E951 in Europe.

Chemical Structure

A white, crystalline, odourless powder. Composed of two amino acids; aspartic acid (40%) and phenylalanine (50%), with a methyl ester bond (10% methanol) Very stable in its dry state1. At 105 centigrade a loss of approximately 5% (conversion to DKP) occurred after 100 hours of treatment. At 120 centigrade a 50% loss is obtained after 80 hours. Degradation in solution depends on pH, buffer concentration and,2. Decomposition products also vary depending on temperature, they are L-aspartic acid (Asp), L-aspartylphenylalanine (Asp-phe), L-Phenylalanine methyl ester (PME), L-phenylalanine (Phe), 3,6-Dioxo5-phenylmethylpiperazine acetic acid (DKP)3 beta-aspartame 4 In a buffer solution of phosphate citrate, the degradation is slightly slower at pH2 than at pH4. At between pH2 6 the major degradation product is L-Phenylalanine methyl ester5, although it has previously been reported to be DKP6. When repeated at 25 centigrade the result remained that PME was the major product. At pH 7 to 10, the major product is DKP and at pH12 it is L-Aspartylphenylalanine (Asp-Phe) 7 In solution at 30-80 centigrade it degrades into DKP8, this leads to loss of sweetness and makes it unsuitable for use in cooking and other high temperature uses. Breakdown of methyl part of aspartame in small intestine when encounters enzyme chymotrypsin. Absorption is speeded up with the ingestion of free methanol, which is created if aspartame is heated to 30 degrees c (86 Fahrenheit). Methanol is broken down to formaldehyde by alcohol dehydrogenase in the liver9. In turn this formaldehyde is converted to formic acid by aldehyde dehydrogenase in liver and by formaldehyde dehydrogenase in the blood.

Uses

Aspartame is classed as a non-nutritive sweetener (i.e. offers no nutritional energy) as its nutritional value is negligible at approx. 4 kcal/g from metabolisation of amino acids. It is high intensity sweetener, which is 160-220 times sweeter than sugar, thus requires little volume to produce sweetness. It was approved by the FDA for dry use, chewing gum and carbonated drinks in 1981, and for general use in 1996. It is approved for use in over 100 countries, and by organisations such as the World Health Organisation, EC scientific Committee on Foods and the European Parliament. It is found in over 6000 products including puddings, frozen desserts, carbonated soft drinks (70% of demand), breath mints, vitamins and cold preparations. In most products it is combined with either sugar or saccharine, but the trend is towards its use

References

1 OBrien, Nabors & Gelandi 1991 2 Hough et al, 1979, Holmer 1984, Prudel et al 1986, Bell & wetzel 1995 3 Furda et al 1975, Tsang et al 1985, Prodolliet & Bruelhart 1993 4 Lawrence 1987, Stamp 1989b 5 Pattanaagson, Chuapradit& Sriskphonraruk, 2001 6 Prodolliet & Bruelhart, 1993 7 Pattanaagson, Chuapradit& Sriskphonraruk, 2001 8 Pattanaargson et al 2000 9DHHS 1993a, Liesivuori 1991

as the sole sweetener in processed foods, for example Pepsi & Coca-Cola have announced that they will use only aspartame in their soft drinks. World-wide sales of aspartame have risen from 72 million dollars in 1981 to 800 million dollars in 2001, with 50% of consumption being in the United States 10 Aspartame is marketed particularly at slimmers, due to its low calorific value, and at diabetics as it is claimed to satisfy sugar cravings without affecting blood sugar levels and is recommended by the American Diabetic Association. It is claimed be free from any side-effects in the majority of people, though it must be used with care in those suffering from PKU, a rare genetic disorder (we will discuss later).

History

The history of aspartame is extremely controversial, with claim and counter-claim being made by the manufacturers and a number of, mainly, Internet sites as to the safety of aspartame. Each side argues the validity and objectivity of its own research, and the inaccuracy and bias of the other side. It has been extensively tested but still doubts remain as to its safety, or otherwise. Aspartame was discovered by James Schlatter, a chemist at G.D. Searle in 1965. While testing a peptic ulcer drug Schlatter spilt some on his fingers and, on licking it off, found the substance to be incredibly sweet. In 1967 G.D. Searle began the safety tests required by the FDA for approval of food additives. 11Dr Harold Waisman, a biochemist at the University of Wisconsin, conducted safety tests on infant monkeys on behalf of GD Searle. Seven monkeys were fed aspartame mixed with milk, of these 1 died after 300 days and 5 had grand mal seizures 12The results of this experiment were not submitted to FDA until 18th August 1985, 27 months after aspartame was approved for dry use. Searle maintained that it had been overlooked13 In November 1970 Cyclamate, the leading brand of low-calorie sweetener was withdrawn due to a suspected link with cancer. At the same time the safety of saccharine was being questioned, leaving the field open for a new sugar substitute. In the Spring of 1971, the neuroscientist, Dr John Olney (whose work on the effects of Monosodium glutamate resulted in it being removed from baby foods) informed GD Searle that his studies had revealed that aspartic acid caused holes in the brains of baby mice. These results were replicated by one of Searles own researchers in a similar study. Searle applied for FDA approval in February 1973, submitting more than 100 studies to support its claims that aspartame is safe. The FDA reviewed this data but on the 5th of March 1973 stated that the information provided (by Searle) is inadequate to permit an evaluation of the potential toxicity of aspartame and calls for further clinical tests. However, on the 26th July 1974 the FDA granted first approval for use in dry goods. In August Jim Turner & Dr. John Olney filed first objections to aspartame approval on safety ground, and in December 1975 the FDA stayed approval until Searles safety studies could be audited 14 The Turner & Olney petition triggered a FDA investigation in March 1976, looking at the laboratory practices at GD Searle. The investigation found Searles testing procedures shoddy, inaccurate and with manipulated test results (15). On the 10th January 1976, the FDA formally requested that US attorneys office to begin grand jury proceedings to investigate whether indictments should be filed against Searle for concealing material facts and making false statements in aspartame safety tests. With grand jury proceedings underway Sidley & Austin, the law firm representing G.D. Searle, begin job negotiations with U.S. attorney in charge of the investigation, Samuel Skinner on the 26th of January 1977. It is worth noting that Skinners wife already worked for Sidley & Austin. Sam Skinner left the District attorneys Office to take up his new position on the 1st of July 1977; he later went on to be the White House Chief of Staff under George Bush. It is claimed that Skinners resignation and subsequent departure led to the drawing out of the case until, on the 8th December 1977, the statute of limitations on aspartame charges runs out and the grand jury investigation is dropped.

10S. Bizzari, M. Jackel, Y. Yoshida. High Intensity Sweeteners. In: Chemical Economics Handbook. Menlo Park, California, SRI Consulting 1996 11 www.swankinturner.com/hist 12 www.swankinturner.com/hist 13 www.psrat.org/aspartame 14 40. Fed.Reg. 56907 Dec.5, 1975 15 www.swankin-turner.com/hist

In the meantime, GD Searle hire prominent Washington insider, Donald Rumsfeld as CEO in an attempt to turn the company around. Then, on the 1st August 1977, The Bressler Report, compiled by FDA investigators and headed by Jerome Bressler, is released. It finds that in one report 98 of the 196 animals died during one of Searles studies but werent autopsied until up to a year after death. Many other inconsistencies are found, including one rat being reported as dead, then alive, then dead again, and a mass, a uterine polyp and ovarian neoplasms were found in the animals but not reported by Searle. On 1st June 1979 The FDA established a Public Board of Enquiry with a remit to rule on the safety issues surrounding aspartame. The panellists were Peter Lampert, Professor & Chairman of the Department of Pathology at the University of California, Vernon Young, PhD of the University of Nutritional Biochemistry at MIT, and Walle Nauta, MD, PhD, Institute Professor of the Department of Psychology at MIT. Dr Olney objected to Dr Youngs appointment as he suggested that Young was unqualified in neuropathology and would therefore be unable review aspartic acids neurotoxicity. However his objections were overruled and the panel was maintained. The panel were told to assess the safety of aspartame only in dry goods, Dr Nauta has stated that he would definitely have considered other tests and factors if he had known that aspartame was planned for use in soft drinks 16. The PBOI concluded unanimously, in September 1980 approval should not be given until further investigation had taken place into possible brain tumours in animals. The board states that it has not been presented with proof of reasonable certainty that aspartame is safe for use as a food additive. However on the 21st January 1981, Ronald Reagan was sworn in as the new President of USA. Reagans transition team, including Donald Rumsfeld (CEO of GD Searle), handpicked Dr Arthur Hull Hayes to be new FDA commissioner. In March 1981an FDA commissioners panel was established to review issues raised by PBOI. This panel (consisting of Dr Robert Condon, Dr Satya Dubey & Dr Douglas Park, 3 of the 6 in-house FDA scientists) advised against approval of aspartame, stating that the Searle tests are unreliable and not adequate to determine approval17. On the 1st July 1981 Dr Hayes, the new FDA commissioner, ignored the PBOI and the recommendation of his internal FDA team, and approved aspartame for dry use. Hayes stated that aspartame has been shown to be safe for its intended use and says that few compounds have withstood such thorough testing and repeated close scrutiny. This conclusion was based on a Japanese report that the other PBOI panellists had not had access to. The PBOI chairman, Dr Nauta later wrote to Dr Hays that if the panel had had access to this information they would have given aspartame unqualified approval18 On the 15th October 1982, the FDA 19announced that Searle has applied for approval as a sweetener in carbonated drinks, other liquids, and childrens vitamins. This was followed on the 1st July 1983 by a request by the National Soft Drink Association (NSDA) to the FDA to delay approval pending further testing, as aspartame is very unstable in liquid form. When liquid aspartame is stored at 85 degrees + it breaks down into DKP and formaldehyde, both known toxins. When FDA approval is granted on the 8th July 1983, the NSDA files an objection and requests a hearing, stating that Searle has not provided responsible certainty that aspartame and its degradation products are safe for use in soft drinks. On the 8th August 1983 Jim Turner of Community Nutrition Institute and Dr. Woodrow Monte, Director of Food Science and Nutritional Laboratories at Arizona State University, filed suit with the FDA objecting to approval on the grounds of unresolved safety issues. This is denied by the FDA20 In September 1983 the FDA commissioner Hayes resigns under a cloud of controversy about his taking unauthorised rides in the private jet belonging to General Foods, a major customer of NutraSweet. Burson-Marsteller, Searles PR firm immediately hired Hayes as a senior scientific consultant. Further objections to the use of aspartame in soft drinks are filed by the Arizona Dietetic Association, the Central Arizona Dietetic Association on the 9th December 1983, as is a supplement to Dr Woodrow Montes previous objection. The objections are denied by the FDA in February 1984 on the grounds that they fail to raise any genuine or substantial issue of fact 21

16 Graves 1984, S5503 of Congressional Record 1985a 17 www.swankin-turner.com/hist 18 www.fda.gov/bbs/topics/answers/ans00772.html) 19 Gordon, 1987 page 499 of US Senate 1987 20 48 Fed.Reg 52899, Nov 16th, 1983. 21 49 Fed Reg. 6672, Feb 17th, 1984

In 1984, it is claimed that the FDA told its regional offices not to report aspartame toxicity to its Washington D.C. headquarters 22. These claims are repeated on the 3rd November 1987, when James Turner of the Community Nutrition Institute gave testimony to the U.S. Committee on Labour & Human Resources that the FDA redirected calls regarding aspartame reactions to the AIDS Hotline. 1985 was a mixed year for G.D.Searle, with the company being bought by Monsanto and a number of further reviews into aspartame safety. The FDAs review but failed to find a consistent pattern of symptoms.23, and The Council of Scientific Affairs of American Medical Association stated Available evidence suggests that consumption of aspartame is safe and not associated with serious adverse health effects. However, in March in Congressional Record, Dr Wurtman, MIT stated, Aspartame has been demonstrated to inhibit the carbohydrate induced synthesis of the neurotransmitter serotonin. Serotonin blunts the sensation of craving carbohydrates and this is part of the bodys feedback system that helps limit consumption to appropriate levels. Its inhibition by aspartame could lead to anomalous result of a diet product causing increased consumption of carbohydrates In 1996 the FDA granted approval for aspartame to be used in all food & beverages. In order to do this without public notification, the FDA would have to show that they are receiving fewer complaints. The FDA told the Wall Street Journal that they have had only 11 complaints, however it is claimed that the FDA will not accept any complaints regarding aspartame at all (see 1984, 1987).24). In October 2000 Food Advisory Committee in the UK puts aspartame on agenda for discussion; 500 papers were sent to EC Scientific Committee on Food with a suggestion that this is a sufficient number to review. Review expected early 2002.25(However information is not available at this time). In the same year Monsanto sold all of its aspartame units to an investor group, NutraSweet Co.

Safety & Health Issues

Acceptable Daily Intake set at 40mg/kg body weight/day by WHO committee of Experts on food additives (JECFA), 1980 Underestimated - FDA assessed at 34mg/kg/day intake a 30kg child drinks 2/3 of a 2 litre bottle of diet coke on a hot day = 23mg/kg (99th centile) add one of 6000 other aspartame containing products -> excess of FDA loading dose 26o funded trade organisations such as the American Diabetic Association and the American Dietetic Association 27. (However it is claimed that these agencies are funded by NutraSweet 28 Amino acids and methyl esters found naturally occurring in meats, milk, fruit & veg body handles them like those found in food daily29 Thoroughly tested30) 74 tests submitted to FDA by GD Searle, no problems but 90 independent studies, 83 problems (www.cfs-recovery.org) Aspartic Acid Aspartic acid makes up 40% volume by weight of aspartame. It is claimed that reports of brain damage is built on faulty premise that large amounts of aspartame leads to a build-up of aspartic acid in the blood, which circulates to brain & kills nerve cells by over stimulation. NutraSweet claim that due to the nature of the aspartic acid transport system it doesnt cause any neurotoxilogical effects as, it does not cross the blood-brain barrier and therefore doesnt accumulate in the brain 31. However Ketchner & Hollenbeck (1991) stated that, although this is normally true, at high doses it can cross into the brain, where it acts as an excitatory

22 CNI 1984. Letter from Rodney E.Leonard & James S. Turner of Community Nutrition Institute to Dr Frank E. Young, Commissioner of FDA. Reprinted in congressional record 1985b, page S10841 23 www.foodstandards.gov.uk., 24 www.dorway.com/betty/olney.html 25 www.foodstandards.gov.uk 26 (congressional record, may 7th 1985, pages s5511) 27 www.spunk.org/library/food/sp001157.txt 28 www.dorway.com/betty/olney.html. 29 www.nutrasweet.com 30 www.aspartame-info.com 31 Maher TJ, 1986 neurotoxicology of food additives, Neurotoxicology, 7(2), 183-196

neurotransmitter and, potentially cause brain damage32. High levels of aspartic acid in its unbound form significantly raise blood plasma level of the neurotransmitter, Aspartate. Excess levels of aspartame allow the influx of too much calcium into the cells, which, in turn triggers excess free radicals that kill the cells. Again, the point is made that some parts of the brain are not protected by the blood-brain barrier.33 As aspartame has very similar characteristics to Glutamate (as in Monosodium Glutamate), researchers looked into the effects of combined levels of aspartame and MSG. According to Stegink et al (1980) 34a 200mg/kg body weight dose of aspartame was given resulting in a peak of combined plasma levels of 7mM/100mL. This level is only 1/20th of that necessary to produce brain damage in infant mice35 36. NutraSweet also state that aspartic acid is eliminated through the lungs as CO2 and that even large amounts of aspartame over a long period do not result in large levels of aspartic acid 37, as shown by Stegink (1984) which showed no significant increase in plasma levels of aspartic acid following an orally administered dose of 34mg/kg of body weight of aspartame.38 Brain Lesions/Tumours Aspartame doesnt enter blood stream so cant travel to essential organs; it is broken down into aspartic acid, phenylalanine & methanol. American Cancer Society, FDA, National Cancer Association (www.nutrasweet.com) Brain tumour rates in US risen 17% between 1975 and 1992, in two distinct phases. First in mid-70s, explained by new diagnostic methods. Second 1984, 10% higher rate which has persisted to present. Possibility that is due to aspartame consumption. Not enough evidence exists to prove link, further research needed. Potential risk low as total number of people affected is low. New study shows sudden 10% increase in malignancy and incidence starting 3 years after aspartame introduced. Rise didnt continue, stabilised if larger % of the population not exposed would explain why rates didnt continue to rise. Olney fed to immature rats and found that it destroyed nerve cells in the brain (www.dorway.com/betty/olneyup1). However Olneys research ahs been criticised by a number of scientists (Levy PS, Hedeker D, 1996 Statistical and epidemiological treatment of SEER incidence data; J. Neurpathol. Exp. Neurol.; 55(12),1280)(Linet MS, Ries LA, Smith MA, Tarone RE, Devesa SS, 1999 Cancer Surveillance series: recent trends in childhood cancer incidence and mortality in the United States: J. Natl. cancer Inst.: 91(16), 1382-1390)(Ross JA, 1998 Brain Tumours and artificial sweeteners? Lesson on not getting soured on epidemiology, Med. Pediatr. Oncol., 30(1), 7-8)(Seife C., 1999 Increasing Brain tumour rates: is there a link to deficit spending? J. Neuropathol. Exp. Neurol.; 58(4), 404-405) who claim that the conclusions do no stand if all the data between 1975 and 1992 is taken into account. The frequency did rise from 1975 until the mid-80s and then stabilised, no relationship is given between the exposure of the population to aspartame and the frequency of brain tumours. An increase may be due to a number of factors including better diagnostic methods39 DKP (a breakdown product) is brain tumour agent. Dr Adrian Gross (1985), the late FDA toxicologist said In view of all the indications that the cancer causing potential of aspartame is a matter that has been established way beyond reasonable doubt, one can ask: what is the reason for the apparent refusal of the FDA to invoke the food additive the Delaney Amendment to the Food and Drug and Cosmetic Act? Is it not clear beyond any shadow of a doubt that aspartame has caused brain tumours or brain cancer in animals, is it not sufficient to satisfy the provisions of that particular section of the law?(www.dorway.com/betty/olney).

32 Kretchner N, Hollenbeck CB, 1991 Sugars and Sweeteners, Boca Raton, CRC Press, p. 151-167, 232-237 33 (Baurua J, Bal A, 1995 Journal of the Diabetic association of India; volume 35, no.4 @ www.awod.com/gallery/probono/dorway/barua)

34 Stegink LD, Filer LJ Jnr, 1980, Effect of an abuse dose of aspartame upon plasma and erthyrocyte amino acid levels of amino acids in phenylketonuric Heterozygous and Normal Adult Subjects, Journal of Nutrition Volume 110, p.2216 35 Kretchner N, Hollenbeck CB, 1991 Sugars and Sweeteners, Boca Raton, CRC Press, p. 151-167, 232-237 36 www.elvis.engr.wisc.edu/uer/uer98/author2/content 37 www.nutrasweet.com 38 Stegink LD, 1984 Aspartame Metabolism in humans: acute dosing studies. In aspartame: Physiology and Biochemistry, Stegink LD, Filer L (eds.), Marcel Dekker, New York,509-553) 39 Modan B, Wagener DK, Feldman JJ, Rosenberg HM, Feinlieb M, 1992Increased mortality from brain tumours: a combined outcome of diagnostic technology and change of attitude

towards the elderly American Journal of Epidemiology; 135, 1349-1357.

It is physiologically impossible for aspartame to be carcinogenic digested in GI tract to small amounts of amino acid, aspartic acid and phenylalanine, all of which present in larger amounts in common food aspartame never enters bloodstream no analysis as to whether brain tumour patients ingested aspartame brain tumour rates increasing in those age 70+, most aspartame users young-middle-aged exclusion of data points 1973/4; would show that rate of increase higher pre-aspartame than post no correlation between plotted line for cancer incidence and aspartame use (www.nutrasweet.com/infocenter/medialib/statements/nutrasweetstatement.asp) Depression In a study of 13 depression patients, Walton 40 concluded that administration of 30mg/kg/day for 7 days caused severe side effects, including nervousness, trouble remembering, nausea, depression and malaise and as such depressive patients should avoid aspartame. However 5 non-depressive patients did not show enough difference between placebo and aspartame to be significant. Waltons earlier report in 1986 41 reported a case of epileptic seizure and serious behavioural problems in a woman being treated with anti-depressants who consumed large quantities of tea containing aspartame. (42 Walton states, When aspartame is ingested with a carbohydrate rich meal the usual physiologic increase in tryptophan is blocked while brain levels of phenylalanine and tyrosine are increased. These changes in amino acid neurotransmitter precursors could, I believe, alter indoleamine /catecholamine balance, and thus have a profound effect on mood and cognitiondepressed mood, anxiety, dizziness, panic attacks, nausea, irritability, impairment and concentration Decreased serotonin levels in brain are also thought to cause altered mind state resulting in insomnia, depression, anxiety, panic attacks, hallucinations, suicide attempts, hostility and psychopathic states 43 Diabetes Beneficial to insulin dependent diabetics as satisfies sweet cravings without affecting blood sugar (44) American Diabetic association approves aspartame in moderation for diabetics, increases dietary choice doesnt affect long or short term blood sugar levels (45. Diketopiperazine (DKP) Toxicity According to JECFA (1980)46, the daily acceptable intake of DKP has been established at 7.5mg/kg body weight, this is based on a level of 750mg/kg as established through long-term study on rats divided by safety factor of 100 47. In solution, when stored at temperatures ranging from 30-80 degrees48. Or at pH 5 and above aspartame is progressively degraded into DKP. As not all solutions are pH neutral (e.g. Water =pH7) and aspartame is often used in non-ideal conditions, e.g. in hot tea and coffee, increasing the breakdown of aspartame into DKP, stability in solution is an area that requires further study 49. Soft drinks are mainly acidic (pH

Also, according to Verrett, an FDA toxicologist, it is implicated in uterine polyps and changes in blood cholesterol. 50 Formaldehyde Toxicity Formaldehyde accumulates in body with repeated ingestion, causing immune system & nervous system changes, headaches, poor general health, genetic damage and a number of other health problems 515253. Wantke 1996, showed chronic exposure to formaldehyde caused systemic health problems in children at air concentration of only 0.043 0.070 parts per million.54 Gradual damage to nervous system, immune system, irreversible genetic damage at low-level long term use. Causes retina damage, interferes with DNA replication, causes birth defects 55 Stored in fat cells, swelling of optic nerve & degeneration of ganglion cells in retina Headaches 28.7% of reported aspartame toxicity to U.S. Food and drug administration Adverse Reaction Monitoring System56 Schiffman Duke University, funded by NutraSweet, 30mg/kg body weight (equivalent 10 soft drinks for 70kg/154lb body weight) = no difference in subjective complaints asp v. placebo, placebo group complained of more headaches, statistically significant study57)58). A small double-blind study over 4 weeks showed increase in frequency of headaches after ingestion of 1200mg/d5960) Van Eeden, 1994 30mg/kg in subjects sure that aspartame caused their headaches statistically significant study result; aspartame causes headaches in small number of people aster long term large quantity use61) Koehler (1988) carried out a double-blind study on patients with medical diagnosis of migraine. After a period of tracking their headaches and diets, a dose of 330mg where given 4 times/day for four weeks. The placebo group had no increase over their baseline level of headaches, whilst approximately half of the subject group had a large increase in numbers of headaches 62 Hyperactivity/ADHD Several studies have shown no relationship between aggressive and hyperactive behaviours, thus children with ADHD neednt avoid aspartame63)64(65

50 Testimony of Dr Jacqueline Verrett, FDA toxicologist before the senate Committee on labour & Human Resources, November 1987) 51 Fujimaki, H., et al 1992 Mast cell response to formaldehyde, International Archives of Allergy & Immunology, Volume 98, No.4, page 324-331 52 He, LJ, Jin LF, Jin HY, 1998 Detection of cytogenetic effects in Peripheral Lymphocytes of Students exposed to formaldehyde with Cytokinesis-Blocked Micronucleus Assay Biomedical Environmental Science, Volume 11, No.1, pages 87-92 53 John EM et al., 1994 Spontaneous abortions amongst Cosmetologists, Epidemiology,

Volume 5, No.2, page 147-155 54 www.psrast.org/aspartame 55 (US Court of Appeals for the District of Columbia Circuit, no.84-1153 Community Nutrition Institute & Dr Woodrow Monte, Dr Mark Novich, acting Commissioner, US FDA (9/24/85) 56 DHHS 1997 Summary of Adverse Reactions attributed to Aspartame (1980-

1996)Memorandum from DHHS Technical Information Specialist (HFS-728) to Health Hazard Evaluation Board on June 26, 1997 57 Schiffman S, 1987, Aspartame Susceptibility to headache, New England Journal of Medicine 58 www.aspartametruth.freeservers.com 59 Koehler SM, Glaros A, 1988 The effect of aspartame on migraine headache- New

England Journal of Medicine 1987;317;1181-1185 60 www.aap.org/policy/re9706 61 www.aspartametruth.freeservers.com 62 Koehler SM, Glaros A,1988 The Effect of Aspartame on Migraine Headache, Headache, Volume 28,p10-14 63 Kruesi MJ, Rapoport JL, Cummings EM et al.,1987 Effects of sugar and aspartame on

aggression and activity in children, American Journal of Psychiatry; 144:1487-1490

Magnesium

Magnesium deficiency causes a number of symptoms ranging from high blood pressure, irregular heartbeat, cramps, cold hands and feet and increased risk of heart attack and stroke66. According to Kovatsi & Tsouggas (2001)67aspartame ingestion leads to imbalance in magnesium levels in the body, with accumulation occurring in some organs and tissues (heart, kidneys, lungs, adrenals, hair and blood) and deprivation in others, such as the liver and testes. Aspartame use also decreases the concentration of magnesium in both urine and faeces, thus affecting excretion levels from the body.68

Methanol toxicity

Methanol accounts for 10% of aspartame by weight. Metabolised into formaldehyde, formic acid and CO2. 1 litre of diet drink produces approx. 48mg of methanol whereas a litre of fruit juice contains approx. 20-280mg of methanol. Small amounts of methanol are produced when aspartame is ingested (also in fruit, veg & juice; 1 cup of tomato juice contains 6x more methanol than 1 cup of aspartame sweetened soft drink) needs 240-600 litres (675 1690 cans to produce toxic levels69) Methanol, wood alcohol is toxin methanol = formic acid +formaldehyde formaldehyde is neurotoxin - EPA assessment; methanol is a cumulative poison due to low rate of excretion once it is absorbed recommended max = 7.8mg/day 1 litre of aspartame drink provides 56mg of methanol (www.dorway.com) all natural sources of methanol also provide ethanol, the antidote to methanol toxicity (www.dorway.com) formic acid slowly accumulates in body, inhibits oxygen metabolism (www.dorway.com Ethanol, natural antidote to methanol, found in natural food at concentrations 5 to 500,000 times that of aspartame 70 Trocho et al., 1998, Life Sci, 63(5), 337-349 Radioactive tracer study 10mg/kg given to rats, who have greater aspartame tolerance than humans (Roe 1982; methanol is 10x more acutely toxic in rats than humans) equivalent to 1 or 2 mg/kg aspartame leads causes binding of formaldehyde into tissues forming adducts with DNA in brain, liver & retina cells (7172. This leads to the conclusion that repeated ingestion may lead to problems with toxicity and carcinogenicity over the longer term. Criticisms levied at this report are that high doses have not lead to liver cancer in rats, and that Trocho did not identify the radioactivity found in the proteins and DNA 73 Parkinsons Disease Mission Impossible International & Aspartame Consumer Safety Network, FDA have received numerous reports of aspartame worsening Parkinsons74 possibly due to effects of excitotoxins in combination with

64 Shaywitz BA, Sullivan CM, Anderson GM, Gillespie SM, Sullivan B, Shaywitz SE, 1994 Aspartame, Behaviour and cognitive function in children with attention deficit disorder, Pediatrics;93;70-75 65 www.aap.org/policy/re9706 66 James B. Pierce, Ph.D., Heart Healthy Magnesium; your nutritional key to cardiovascular wellness 67 Kovatsi L, Tsouggas M The effect of oral aspartame administration on the balance of magnesium in the rat Magnes Res., September 2001; 14(3):189-94 68 www.alkalizeforhealth.net/lsweetdebate24 69 www.nutrasweet.com 70 Monte WC, 1984 Aspartame: Methanol, and the Public Health, Journal of Applied Nutrition, vol.36 (1); 42-54 71 www.presidiotex.com/barcelona/index.html 72 www.alkalizeforhealth.net/Lsweetdebate10.html 73 Tephly TR, 1999 Comments on the purported generation of formaldehyde and adduct formation from the sweetener aspartame, life sci.:65(13), 157-60 74 Stoddard, Mary Nash of Consumer Safety Network, 1995

formaldehyde metabolite excitotoxins implicated in development & worsening of Parkinsons symptoms75 alt. theory by Pardridge, (1986) free-form (i.e. unbound to protein) phenylalanine is absorbed quickly and can spike levels of aspartame in the blood76)(77)(78). This sudden rise in phenylalanine levels interferes with L-DOPA used to treat Parkinsons patients 79 Karstaedt 1993 states, Aspartame consumption in amounts well in excess of what is consumed by heavy users of aspartame-sweetened products has no effect on PD (Parkinsons Disease) patients 80Criticisms of this research: 1. Study only lasted 1 day. Neurological effects of aspartame use usually take middle to long-term use to appear in patients81822. Aspartame was given in capsules, which has been proven to eliminate sudden absorption of aspartame breakdown products)83 Since the experiment was designed to test whether the spike of phenylalanine effected Parkinsons patients, it was necessary that this spike occurred not eliminated. 3. The claimed high dose of aspartame given was 20 40% of the FDA acceptable daily level of 50mg/kg/day. The estimation was based on projected of aspartame intake published shortly after aspartame was licensed for use in carbonated beverages 84 85 Phenylalanine / Phenylketonuria (PKU) Phenylalanine makes up 50% by weight of aspartame. It is claimed that although some phenylalanine is excreted as CO2, most is incorporated into the pool of amino acids where it is used for protein synthesis However the adverse neurological effects of aspartame may be due to phenylalanine. The ability of phenylalanine to reach brain differs depending on whether it originates from aspartame or from dietary sources8687 .In aspartame the phenylalanine is in free-form, i.e. not bound to protein, it is absorbed quickly and can spike blood plasma levels of phenylalanine888990. This rush does not occur when ingesting food as protein is

75 Blaylock, R Excitotoxins: The taste that kills, 1994, Choi, D. Amyotrophic Lateral sclerosis and Glutamate Too much of a good thing, 1992,Kurland, L.T. Amyotrophic Lateral Sclerosis and Parkinsons Disease Complex on Guam Linked to an Environmental neurotoxin, Trends in Neuroscience, Volume 11, p51-54, 1988 76 Cabarello, B et al Plasma Amino Acid Levels After single dose aspartame consumption in Phenylketonuria , milk hyperphenylalaninemia and Heterozygous State for Phenylketonuria, Journal of Paediatrics, volume 190, No.4 p. 668-671, 1986 77 Matalon, R et al aspartame Consumption in Normal Individuals and Carriers for Phenylketonuria, presented at Dietary phenylalanine and Brain function, 1987 and reprinted

in Dietary Phenylalanine and Brain Function, 1988, Birkhauser, Boston, MA, USA, p 41-52 78 Stegink, LD et al Plasma Amino Acid Concentrations in Normal Adults Administered Aspartame in Capsules or Solution: Lack of Bioequivalence Metabolism, volume 36, No.5, p 507 512 79 Pardridge, WM Potential Effects of the Dipeptide sweetener Aspartame on the Brain, Nutrition and the Brain, volume 7edited by R.J.Wurtman and J.J. Wurtman, raven Press, NY,

1986 p. 199-241 80 Karstaedt, P, Pincus J, Aspartame Use in Parkinsons Disease, Neurology, Volume 43, p 611 613 81 CDC Evaluation of consumer Complaints Related to Aspartame Use, Division of Nutrition, Centre for Health Promotion and Education, centres for Disease Control , Atlanta, GA 30333, November 1984 82 Roberts HJ Reactions attributed to aspartame-Containing Products: 551 Cases, Journal of Applied Nutrition, Volume 40, page 85-94, 1988 83 Stegink, LD et al Plasma Amino Acid Concentrations in Normal Adults Administered Aspartame in Capsules or Solution: Lack of Bioequivalence Metabolism, volume 36, No.5, p 507 512. 84 Roak Foltz R., Leveille G. Projected Aspartame Intake: Daily Ingestion of Aspartic Acid,

Phenylalanine and Methanol in Stegink, L., Filer, L., 1984 Aspartame: Physiology & Biochemistry, Marcel Dekker Inc., NY 85 www.holisticmed.com/aspartame/abuse/parkinson.html 86 Maher TJ, 1986 2Neurotoxicology of food Additives, Neurotoxicology, 1986, 7(2), 183-196 87 Maher TJ, Wurtman RJ,1987 Possible Neurological effects of aspartame, a widely used food additive. Environ. Health Perspect., 75;53-57 88 Cabarello 1986

broken down slowly and phenylalanine is absorbed gradually, however according to Wurtman and Walker ingesting aspartame with carbohydrates can lead to excess levels of phenylalanine in brain 91. Nor does this rush occur when aspartame is ingested in capsule form.92 . With aspartame consumption there may be a competition with other amino acids at the blood-brain barrier, thus aspartame ingestion may lead to higher than normal levels in the brain (unless consumed with food). This is supported by Wurtmans (1985) findings that increased phenylalanine in the brain may affect synthesis of catecholamines or serotonin, causing convulsions 93 94. This may cause special problems for those suffering from PKU or epilepsy. PKU, is a rare genetic disorder, which prevents phenylalanine being metabolised, allowing it to build up to harmful levels in the blood. It is an inherited condition that occurs in 1 in 15,000 babies. A programme of screening at birth allows early detection and the baby is put on a restricted diet in order to control the condition. There are two types of PKU: 1. Homozygous PKU, that is genes inherited from both parents leads to irreversible mental retardation

within the first few months of life if undetected. 2. Heterozygous PKU is derived from only one parent. They show no signs of PKU but metabolise

phenylalanine at 50% if the rate of normal human beings. In the Kretchmer & Hollenbeck (1991) study, 12 normal men & woman and 8 heterozygous women were given 34mg/kg of aspartame in one serving after a period of fasting. The resulting levels of phenylalanine in the blood were only 5mM/100ml higher for the heterozygous subjects, a level that would not cause a risk to PKU heterozygous individuals. 95

These decreased levels of serotonin, due to excess phenylalanine, are also implicated in other symptoms such as depression (see Depression, p.5) and carbohydrate cravings. (See Weight Gain & Appetite, p.8)

Seizures/Epilepsy

According to 1995 figures, 7% of aspartame toxicity reactions reported to FDA involve seizures or convulsions 96. Many studies have indicated the role of aspartame in migraines. Roberts (1988) studied 551 patients who claimed a reaction to aspartame, in 18% of cases grand mal, petit mal and absence seizures occurred97) Camfield (1992)98 administered a single dose of 40mg/kg of aspartame mixed in liquid to children with generalised absence epilepsy. The conclusion drawn was that aspartame appears to significantly increase the

89 Matalon Reuben et al, 1988 aspartame consumption in Normal Individuals and carriers for Phenylketonuria (PKU), presented at dietary phenylalanine and Brain Function.

Proceedings of the first International meeting on Dietary phenylalanine and Brain Function, Washington DC, May 8-10, 1987. Centre for Brain Sciences & metabolism Charitable Trust , PO Box 64, Kendall square, Cambridge, MA 02142. Reprinted in Dietary Phenylalanine and Brain Function, c1988, Birkhauser, Boston, MA, USA, page 41-52 90 Stegink, LD., 1987 Plasma amino acid Concentrations in Normal adults administered aspartame in capsules or solution: lack of Bioequivalence, metabolism, volume 36, no.5,

pages 507-512 91 (Wurtman & Walker Dietary Phenylalanine and Brain Function Proceedings of the first International Meeting on Dietary Phenylalanine & Brain Function, Washington DC, may 8 10 1987) 92 Stegink, LD., 1987 Plasma amino acid Concentrations in Normal adults administered aspartame in capsules or solution: lack of Bioequivalence, metabolism, volume 36, no.5,

pages 507-512 93 Wurtman RJ, 1985aspartame;possible effect on seizure susceptibility The Lancet, 9(2), 1060 94 www.afssa.fr/ftp/basedoc/aspartamgb.pdf 95 Kretchmer N, Hollenbeck CB, 1991 Sugars and Sweeteners, Boca Raton, CRC Press, p. 151-167, 232-237 96 DHHS 1995, Department of Health and Human Services. Report on all adverse reactions in the Adverse Monitoring System, 20th April 1995 97 Roberts HJ , 1988 Reactions Attributed to Aspartame-containing products: 551 cases, Journal of Applied Nutrition, Volume 40, pages 85-94 98 Camfield PR, Camfield CS, Dooley JM, Gordon K, Jollymore S, Weaver DF, 1992 Aspartame exacerbates EEG spike-wave discharge in children with generalised absence

epilepsy; a double blind controlled study Neurology:42; 1000-1003

duration of time that children with absence epilepsy have spike-wave on their EEG. In this study children spent 40% more time in spike wave after aspartame than after sucrose. Subjects were not on anti-seizure medication during study, authors called for longer study to take place. US Air Force & Navy also acknowledge the effects of aspartame. Articles have been published in both Flying Safety and Navy Physiology magazines, warning that aspartame ingestion may make pilots more susceptible to seizures and vertigo 99 Increased levels of phenylalanine along with increased ration of phenylalanine to other Large Neutral Amino Acids can inhibit enzymes needed to synthesise neurotransmitters and diminish the production of brain catecholamines and serotonin. The hypothesis is that this change in blood chemistry leads to lowering of the seizure thresholds, therefore those ingesting aspartame become more susceptible to seizures 100 Several animal studies have shown that aspartame lowers the seizure threshold in animals101102 103104105106, though these results are based upon Wurtmans findings that a dose of 60x more aspartame is needed in rodent studies to stimulate changes in phenylalanine/LNAA ratio that occurs in adults107. However this finding is challenged by Hjelle (1992). Based on Wurtmans findings several teams have found that aspartame lowers the seizure threshold in animals A number of other scientists have refuted the claims that aspartame causes seizures (108)(109). In a Monsanto/NutraSweet funded study, Shaywitz 110concludes, our findings indicate that, in this group of vulnerable children, APM (aspartame) does not provoke seizures. This study is criticised as 9 out of 10 children were taking anti-seizure medication at the time, the dose was given in capsule form (thus eliminating

99 US Air Force, 1992 aspartame alert, Flying safety 48(5):20-21 (may 1992) 100 Maher, TJ, Wurtman, 1987 Possible Neurologic effects of aspartame, a widely Used Food

Additive, environmental Health Perspectives, volume 75, page 53-57. 101 Diomede L et al., 1991 Interspecies and Interstrain Studies on the Increased to Metrazol-Induced Convulsions in Animals Given Aspartame Food and Chemical Toxicology, Volume 29, 101-106 102 Garrattini S et al., 1988 studies on the susceptibility to Convulsions in Animals Receiving abuse Doses of aspartame, presented at dietary phenylalanine and Brain Function.

Proceedings of the first International meeting on Dietary phenylalanine and Brain Function, Washington DC, May 8-10, 1987. Centre for Brain Sciences & metabolism Charitable Trust , PO Box 64, Kendall square, Cambridge, MA 02142. Reprinted in Dietary Phenylalanine and Brain Function, c1988, Birkhauser, Boston, MA, USA, page 131-143)(Guiso G et al., 1988 effect of aspartame on Seizures in various models of experimental Epilepsy, toxicology & applied

Pharmacology, volume 96, No.3, pages 485-493 103 Kim KC, Tasch MD, Kim SH, 1988 The Effect of aspartame on 50% Convulsion doses of Lidocaine, , presented at dietary phenylalanine and Brain Function. Proceedings of the first International meeting on Dietary phenylalanine and Brain Function, Washington DC, May 8-10, 1987. Centre for Brain Sciences & metabolism Charitable Trust , PO Box 64, Kendall square, Cambridge, MA 02142. Reprinted in Dietary Phenylalanine and Brain Function,

c1988, Birkhauser, Boston, MA, USA, page 127-130 104 Maher TJ, Wurtman R, 1987 possible Neurologic Effects of Aspartame, a Widely Used Food Additive, Environmental Health Perspectives, volume 75, page 53-57 105 Pinto JMB, Maher TJ, 1986 High Dose aspartame Lowers the Seizure Threshold to subcutaneous Pentylenetetrazol in Mice, The Pharmacologist, volume 28, page 155 106 Pinto JMB, Maher TJ, 1988 administration of Aspartame Potentiates Pentylenetetrazole-

and Fluorothyl-Induced seizures in mice, Neuropharmacology, volume 27, No.1, page 51-55 107 Wurtman RJ, Maher TJ, 1988 General discussion: calculation of the aspartame dose for rodents that produces neurochemical effects comparable to those occurring in people,

Dietary Phenylalanine and Brain Function. Proceedings of the First International Meeting on

Dietary Phenylalanine and Brain Function, Washington DC, May 8 10, 1987. Centre for brain

science and metabolism charitable trust, PO box 64, Kendall square, Cambridge, ma 02142.

Reprinted in dietary Phenylalanine and Brain Function c1988, Birkhauser, Boston, MA, USA 108 Anderson GM, Novotny EJ, Shaywitz BA,1996 Evaluation of seizures in: The Clinical Evaluation of a food additive. Assessment of aspartame, Tschanz C, Butchko HH, Stargel WW, Kotsonis FN(edts), 1996, pp 205-216, CRC press, Boca Raton, New York, London, Tokyo 109 Gaull GE, 1985 Aspartame & Seizures, lancet: 2(8469-70),1431 110 Shaywitz BA et al., 1994a Aspartame Has No Effect on Seizures or Epileptiform Discharges

in Epileptic Children, Annuls of Neurology, volume 35, pages 98-103

the blood plasma phenylalanine spike, which is thought to be partially responsible for causing seizures) 111Also the tests were carried out on epileptic children who had not reported aspartame-induced seizures.112 Rowen (1995)113concludes aspartame, in acute dosage of ~50mg/kg is no more likely than placebo to cause seizures in individuals who reported their seizures were provoked by aspartame consumption. Criticisms of this report are that 16 of the 18 subjects were on anti-seizure medication at the time of the study. Again, the aspartame was given in capsule form so the phenylalanine was ingested slowly as it would be if it was ingested in food. Capsule administration also slows the absorption of both methanol, reducing the effects of methanol toxicity (Posner 1995) and aspartic acid, which when absorbed quickly may be an excitotoxin 114Significantly, there was only one dose of aspartame given. Neither the fact that aspartame was given in capsule form nor that the subjects were on medication was given in the abstract of this study.115 Trefz (1994)116reports that doses of 15mg/kg and 45mg/kg of aspartame in PKU heterozygotes does not change EEG spectral parameters. Again the aspartame was given in capsule form, and in this case it was given with meals both of which would delay the absorption of the aspartame breakdown products. This study was longer term than Rowen and Shaywitz, lasting 3 months. However analysis of seizures linked to aspartame doesnt usually appear until after 3 months of non-encapsulated aspartame 117(118 The FDA report in 1992 119concluded, In most cases, information obtained from the complainants medical records as well as data on consumption patterns, temporal relationships, and challenge tests did not support the claim that occurrences of the seizures were linked to consumption of aspartame. The criticisms levelled at this report are that unclear cases (e.g. medical records not released, any lifestyle factors, for example smoking, or stress, which may influence health) were classified as Group D highly unlikely, and it is suggested that a category such as possible aspartame reaction may be more appropriate. Also any reactions that took place more than 13 hours after ingestion (35% of the non-Group D seizure patients), however Carroll (1992)120 puts forward that reactions to food intolerance can be exhibited up to 48 hours after ingestion, and that excitotoxins can remain in the brain for up to 24 hours121. The report also states that only 251 cases of seizures due to aspartame ingestion have been reported to the FDA, however there are actually 5 categories: seizures and Convulsions, Grand Mal, Petit Mal, complex Partial seizures and Simple Partial Seizures, and the 251 quoted cases are only those in the seizures and Convulsions Category. Of the final result 76 of the 251 cases were classified into Groups A and B, meaning that a re-challenge with aspartame lead to further seizures.

111 Stegink, LD., 1987 Plasma amino acid Concentrations in Normal adults administered

aspartame in capsules or solution: lack of Bioequivalence, metabolism, volume 36, no.5, pages 507-512. 112 www.holisticmed.com/aspartme/abuse/seizures 113 Rowen ., James, A., Shaywitz et al., 1995) aspartame and Seizure Susceptibility: Results of a Clinical Study in Reportedly Sensitive Individuals, Epilepsia, Volume 36, No.3, page 270-275) 114 Blaylock, RL., 1994 Excitotoxins: the Taste That Kills, Health Press, Santa Fe, New Mexico,

c1994 115 www.holisticmed.com/aspartame/abuse/seizures. 116 Trefz F., de Sonneville, L, Matthis, P., Benninger C., Lanz-Englert B., Bickel H., 1994) Neuropsychological and Biochemical Investigations in Heterozygotes for Phenylketonuria During Ingestion of High Dose Aspartame (A Sweetener containing Phenylalanine), Human Genetics, Volume 93, page 369-374 117 CDC (centre for Disease Control), 1984 Evaluation of Consumer Complaints Related to Aspartame Use, division of Nutrition, Centre for Health Promotion and education, Centres for disease Control, Atlanta, GA 30333, November 1984 118 www.holisticmed.com/aspartame/abuse/seizures 119 Tollefson L., Barnard RJ, 1992 An Analysis of FDA Passive Surveillance Reports on seizures Associated with Consumption of Aspartame, Journal of the American Dietetic Association,

Volume 92, No.5, page 598-601 120 Carroll P, Caplinger K, France G, 1992 Guidelines for Counselling Parents with Young Children wit Food Sensitivities, Journal of American Dietetic Association, volume 92, No.5, page 602-603 121 Inouye, M, 1976 selective distribution of radioactivity in the Neonatal Mouse Brain Following the Subcutaneous Administration of 14 C-labelled Monosodium Glutamate,

congenital Anomalies (Journal serial No. 0914-3505, Japan),Volume 16, page 79-84

Animal studies showing that aspartame does not lower seizure threshold:122123124125126127128129These studies show that it takes huge doses of aspartame in order to lower the seizure threshold in rodents and therefore normal doses would not be enough to do it in humans. However this does not take into account Wurtmans (1988) finding that it takes 60x more phenylalanine to cause the phenylalanine/LNAA changes in rats than it does in humans. In a study on newborn monkeys doses of aspartame at 1,3,and 4 g/kg per day were administered for 52 weeks. Epileptic seizures were recorded at highest doses after 218 days of treatment, with sporadic convulsions occurring during handling. Symptoms were identical with those observed in young monkeys treated with phenylalanine. In a later study showed no effect in monkeys treated with 2 and 2.7g/kg/day. Different results could be explained by differences in exposure conditions, food and state of health of the animals 130 Weight Gain & Appetite Aspartame is marketed as being ideal for people following a weight management programme, as it is lower in calories than sugar. However this use of the sweetener was challenged in March 1985 when, in the Congressional Record, Dr Wurtman, of MIT, stated, Aspartame has been demonstrated to inhibit the carbohydrate induced synthesis of the neurotransmitter Serotonin. Serotonin blunts the sensation of craving carbohydrates and this is part of the bodys feedback system that helps limit consumption to appropriate levels. Its inhibition by aspartame could lead to anomalous result of a diet product causing increased consumption of carbohydrates Other Reported Symptoms The following is a list of symptoms attributed to aspartame consumption as reported to the FDA and to Internet sites relating to aspartame use 131. MS symptoms Chronic diarrhoea esp. after meals, severe stomach cramps, abdominal pain, gassy, constipation Dizziness vertigo attacks

122 Cain DP et al., 1989 Failure of aspartame to affect seizure susceptibility in kindled rats, Neuropharmacology, volume 28, No.4, pages 433-435 123 Dailey JW, Lasley SM, Bettendorf AF, Burder RL, Jobe PC, 1988 aspartame does not facilitate Pentylenetetrazol induced seizures in genetically epilepsy prone rats, Epilepsia, volume 29, page 651 124 Dailey JW, Lasley SM, Mishra PK, Bettendorf AF, Burder RL, Jobe PC, 1989 aspartame fails to facilitate Pentylenetetrazol-induced convulsions in CD-1 Mice, toxicology and applied pharmacology, volume 98, pages 475-486 125 Jobe PC, Bettendorf AF, Lasley SM, Daily JW, 1988 Effects of aspartame on Pentylenetetrazol-Induced convulsions in CD-1 mice, Toxicologist, volume 8, page 85 126 Meldrum BS, Nanji, 1988 Lack of Effect of Large doses of aspartame on photically-

induced seizures in the baboon, FASEB journal, volume 2, page A434 127 Nevins ME, Arnolde SM, Haigler HJ, 1986 Aspartame: Lack of effect on convulsant thresholds in mice, Federal Proceedings, volume 45, page 1096 128 Thai L, Tilson HA et al., 1988 lack of Effect of aspartame on Kindling, Electroconvulsive shock (ECS) and Metrazol-induced seizures in rats, society of Neuroscience Abstracts, volume 14, page 866 129129 Tilson HA, Thai L, et al., 1989 Oral administration of aspartame is not proconvulsant in

rats, Neurotoxicology, volume 10, pages 229-238 130 JECFA,1980 Toxicological evaluation of certain food additives: aspartame WHO food additive series No.15, Report series No.653 131131 www.holisticmed.net/aspartame/adverse.txt

Depression manic depression anxiety attacks morning anxiety Low energy levels, very chronic fatigue, weakness esp. legs, fatigue, CFS Cold sweats Short term memory loss, memory loss, poor memory, inability of concentrate, forgets what is saying in middle of sentence, feels like fog has been lifted (on giving up), confusion Tremors, head shaking Weight gain, bloating, and obesity Chronic cough, sneezing Breathing difficulties, asthma, breathlessness, and temporary inability to breathe Burning urination, urinary infections Face flushing Thinning hair, lost hair Loss of sexual feelings messed up menstrual cycle - PMS Irritability Itching, numbness, tingling of extremities Joint pain sever pain of shoulders, hips, and knees Tachycardia hypertension, heart palpitations cardiac arrest Insomnia, sleep disorders, fear of going to sleep in case dies of seizure Tripping, falling, balance problems, legs give out Craves sweets food cravings feeling of being full all the time though would hardly eat, excessive hunger or thirst Slurred speech Drooping mouth, muscle spasms, Bells Palsy, loss of muscular power in one side of face Acne, rashes Blurred vision poor vision temporary loss of vision hard to focus, lights flashes in eyes, dry eyes Back pain Allergies Chest pains Swollen feet Feeling old (repeated symptom) Coma Hallucinations Sore throat, throat inflammation, throat closes up; feels like choking; cant get breath Bleeding gums, sore mouth, dry mouth Ringing in ears poor hearing Sweating Birth defects Addiction ADHD, aggravates autism

MIND

ORGANISED/PRODUCTIVITY: 001 00.01.10 I have just been & tidied up my study, put away all my books & changed bedding - jobs I'd

been meaning to do for the last few days. Unusual for me to do this before work. 001 01.15.xx Wide awake, had urge to do tidying up in kitchen drawers but did not because everyone

else asleep 003 02.01.xx Feel surprisingly calm despite a multitude of extra tasks involved in getting my child to

school; everything seems to run like clockwork, which is unusual I would normally get very impatient.

005 02.01.xx Still feel sense of well-being. Think I have dealt with my busy day better than usual, by just being busy and not stressed.

003 02.05.xx Still feel very calm despite having to organise a birthday party. The calm feeling continues through the party, despite a (minor) injury to one of the children, which would normally make me feel quite stressed.

001 02.xx.xx In morning felt calmer than usual and have done more housework 005 03.01.xx Dealing well with problems at work today and energy level seems unusually high. 001 04.09.xx Energy level high for a Friday afternoon; have been quite efficient, sorted out some bank

stuff, got washing done, etc. 004 05.02.xx Need to get a move on and be organised, dont have usual sense of urgency, feel laid back. 005 06.03.xx In general feel better able to deal with things and a weight has been lifted off me. 004 03.13.xx Also feeling better for having practical things to do and moving about 005 10.xx.xx Not much happening, but generally feeling happier and dealing with things in general better. FORGETFUL/MISTAKES: 003 02.02.xx Forget to take childs lunchbox and book bag to school and have to make a

return journey. Have never done this before. 001 02.xx.xx Whilst doing research at Record Office, have not worked through in my

usual methodical way at all. (Some of this kind of research is quite time-consuming, involving carefully looking through each register until the correct person is found) I moved from one thing to another, too impatient. Research has to be repeated as unreliable! I noticed this only in retrospect - when I came back to look what Id done - it was such a mess, all over the place!

006 02.xx.xx Was in the process of sending a text message to my partner and completely forgot what I was going to text. Sat for about 15 minutes and still couldnt remember usually have a good memory.

006 03.xx.xx I cant seem to collate all the information in my head. 006 03.xx.xx I feel muddled up. I keep forgetting things like I was talking on the mobile

phone while packing up to leave work, but was looking around to try and find where my mobile phone was. Finally realised it was because I was using it.

005 04.08.xx Met friends and didnt feel myself at all and couldnt think of what to say to them or talk properly. They noticed and commented that they thought I was a bit weird. Then I met some other friends and I couldnt remember the names of the people I had just left, which is very uncharacteristic.

005 04.09.xx Spoke to another friend on the phone and wasnt making much sense couldnt understand my own train of thought and it amused my friends.

001 05.10.xx Feel extremely irritable - research at Record Office has to be repeated because what I did last is unreliable. Arrive home wanting to relax but have to prepare dinner etc. Both partner and son seem incredibly unhelpful and slow.

004 05.xx.xx Feeling spaced out and mixing up words, spoonerisms, e.g. said Muddy fore

prints instead of paw prints. Am now clear this has been happening for last 4 days. Am trying to cover this stoned feeling

006 05.xx.xx Lost track of the day number in my proving diary, entries are a bit muddled have to go back and sort it out.

006 07.xx.xx My memory is appalling, I keep forgetting what I am going to say in a conversation

003 08.xx.xx Go to cafe to buy cup of tea and a cake, but realise I have no money when I go to pay. This is the second time this has happened to me in three days. Never happens normally I usually have a very good idea of how much money I have on me.

001 08.xx.xx Not being very productive at work today, not particularly upset about it. Usually I am very conscientious.

004 09.xx.xx Got home to find girls moths tutor had arrived. I had completely forgotten she coming even though we had spoken a few hours earlier.

004 10.xx.xx Suddenly realise I forgot to take the girls to the dentist, and cannot afford cancellation fees. Am normally very well organised about appointments. Am feeling out of it again.

001 10.xx.xx In retrospect I have forgotten to write symptoms in diary after 8.15 a.m. and have re-written an observation already put in the day before. Today I have forgotten to write in diary until the evening

009 11.xx.xx Fleeting sensations of being out of it throughout the day. Forget to pick up a friend to take her shopping. Then became totally focused on one thing instead of her. Went to a party and danced without getting breathless or tired!!

009 13.xx.xx Could not find a text message on mobile and could not organise a meeting, a friend had to do it for me!

004 15.xx.xx Confusion! Keep thinking I have finished a task, e.g. putting on childrens socks and shoes, and I have not! See headache; feel as though the remedy has finished its action, Im tired, worn out had enough and have no joy left. Am still making mistakes with words e.g. said waiting instead of writing

004 19.xx.xx Walking around Brighton and feeling overwhelmed by everything. Am normally enjoying the stimulus. Found myself tuning out, forgot where I had put money, mixing up words.

004 23.xx.xx Spent the day getting words wrong e.g. its time for the dreaded fruit, when I meant food

003 32.xx.xx Still very forgetful and confused (aggravated by severe headache!) I keep failing to notice when people speak to me possibly because I have to focus very hard on what I am doing. In fact, I am still so forgetful that I put my childs coat down in a shopping centre and lose it.

004 44.xx.xx Beginning to feel spaced out and am aware of it, kept repeating conversations and friend had to remind me.

TIME: 001 00.00.40 Feel slightly spaced out, slowed down, but alert, wanting to do things.

Careful. Calm. 003 02.01.xx Everything seems to run like clockwork, which is unusual. 006 05.xx.xx Lost track of the day number in my proving diary, entries are a bit muddled

have to go back and sort it out. 006 05.x.xx I have mixed up all the days and entries in my proving log. I have lost track

of what day it is. I will have to go back and change it. 001 10.40.xx Felt some strange thing happening with time today - I was convinced the

date was the 28th yesterday & reduced items at work accordingly, & got very confused when I found it was still then 28th today. Things seemed to get done more - as if time stretched a bit - within a short space of time, but without any hurrying.

INDIFFERENCE:

009 01:12XX Am not physically tired, but have an overwhelming urge to close my eyes and sleep. I do not want to get the evening meal ready, I cannot be bothered.

004 02:03 Feel like I am slipping back into my own space, cant be bothered to organise group discount for a swim

006 03.xx.xx Things dont affect me much. Something happened at work that would normally make me furious but it has just gone by and I dont seem to care.

003 03.03.xx Decide to go out for a bike ride. Very unusual for me, as I usually sit at home feeling stressed about not getting my college work done when Im not at work.

001 03.05.xx Very calm day at work, not as stressed as usual for a Thursday. As usual lots of complaining people but I don't feel hurried/hassled by them today - just momentarily irritated, can't be bothered with this nonsense.

004 04.03.xx Supervisor arrived and I could not be bothered to give symptoms and have not written them in red book.

006 04.xx.xx Not upset about the meanness of people at work not giving much to a long-serving employees retirement party. Usually would have been very upset by this.

009 05:02 Need to get a move on and be organised, dont have usual sense of urgency, feel laid back.

007 06.xx.xx She has felt better in herself - less irritable and not so argumentative 004 07.xx.xx Visiting a friend and find I am withdrawing into my own world again. Too

much noise and lights seem too bright. When I had had enough, I quietly got the children ready and left (this is normally frantic, stressed out event)

006 10.xx.xx Feel like I cant be bothered with anything. I feel like I am in a bubble with the whole world going on around me.

006 13.xx.xx There was an incident at college, which I would usually have got upset about, but it doesnt bother me at all, which is unusual.

001 12.10.xx After college discussion of proving symptoms, I feel spaced out again - very calm and everything a little surreal - a bit like the start of an LSD trip when you know it's starting to work, but before you get the full effect. I know I have to do some preparation for tutorial tomorrow but really can't be bothered at all - it just doesn't seem important now. Like it's a long way off anyway.

001 13.xx.xx Felt more assertive today at college - couldn't be bothered with some niggly stuff that came up re "group dynamics" - just went and got it sorted out with the people concerned; being straight, direct with them but also seeing funny side of things.

004 16.xx.xx A.m. Notice spaced out feelings have gone and I want them back!! P.M realised that I had been tuning in and out whilst clothes hunting in a charity shop. Had been very laid back looking after 5 children, even though we were on a main, busy road

001 xx.xx.xx Also I dreamt my partner and I were both having diarrhoea - doing it at the same time, together. I had to go and have a shower after, as it was so messy! This was just normal/OK in the dream, not disgusting at all. Made me laugh when I woke up. (I do not often remember my dreams, so it was unusual for me to recall dreaming this much)

CALM, LIGHT AND ALERT: 001 00.12.25 Feel spaced out. Calm, but alert - things seem sharp & clear - like looking

through a rail tunnel - when you come out, everything seems clearer in outline. A bit surreal.

001 01.15.xx Wide awake, had urge to do tidying up in kitchen drawers but did not because everyone else asleep Felt relaxed, alert, happy, no desire to sleep. Read till 12.30 before going off to bed.

003 0201.xx Feel surprisingly calm despite a multitude of extra tasks involved in getting my child to school; everything seems to run like clockwork, which is unusual I would normally get very impatient.

003 02.05.xx Still feel very calm despite having to organise a birthday party. The calm feeling continues through the party, despite a (minor) injury to one of the children, which would normally make me feel quite stressed.

001 02.xx.xx In morning felt calmer than usual and have done more housework. 001 03.12.xx Tired at end of day. Slept for 15mins. In evening then felt more awake,

alert. (Usually if I'm that tired, I just get more tired). 001 03.05.xx Very calm day at work, not as stressed as usual for a Thurs. As usual lots

of complaining people but I don't feel hurried/hassled by them today - just momentarily irritated, can't be bothered with this nonsense.

001 03.xx.xx Felt tired during day, but calm. 04.01.xx Feel good, alert, light-hearted. 006 04.xx.xx Feel mood has improved, is lighter. 006 05.xx.xx Mood still feels lighter. 06.09.xx Mood wise feel normal, i.e. anxious! Looking forward to daughter coming

this evening but can't help background worry about train being late, accidents, etc. Stupid, but can't help it. Feel as if remedy has stopped having an effect - actually from yesterday I think. (In retrospect, this was because I associated the remedy with feeling calm, alert, and happy).

006 06.xx.xx Mood is still improved, still feel lighter than usual. 006 07.xx.xx Mood is still light and feel so much more laid back. 006 08.xx.xx Not being very productive at work, but not worried about it.

Feel great though. Cant believe my mood is so much lighter. Still feeling exhausted though.

DULLNESS/TIREDNESS: 006 01.xx.27 Feel fuzzy headed 007 01.xx.xx She hadnt had time to eat. She went to bed and went straight to sleep.

She had been physically tired all day and she just wanted to sleep. Felt despondent - like she couldnt be bothered (with headache)

007 02.xx.xx Feels a bit daydreamy - like she needs to be shaken to wake up and take notice

006 02.xx.xx Feel mentally dull not achieving much. Feel abnormally tired. Very fuzzy headed a cloudy feeling in the head. Feeling dull and unemotional.

006 03.xx.xx Feel dull all over, mentally and physically. 001 03.xx.xx Felt tired during day, but calm. 004 04.01.xx Alarm went off, I cannot be bothered to get up, am working out when I can

have a lie in. 001 05.14.xx Very tired but no longer irritable. Sleepy 006 06.xx.xx Still feel hung-over. This exhaustion is just so debilitating 001 07.09.xx Feel tired; quiet day at work makes it more tiring. Tired and irritable with

family especially around dinner-cooking time - usual stuff, "I'm doing all the work whilst rest of family relaxing, etc"

006 07.xx.xx Head feels full, heavy, as if a bubble with things going on around it. 004 07.xx.xx Friends tell me I am looking well today and that last week I looked

withdrawn, tired and pale. I am feeling withdrawn and light headed and slightly giggly. By 21.00hrs am feeling very tired, its a heaviness about the eyes that makes me want to close them, cannot study.

006 08.xx.xx Not being very productive at work, but not worried about it. Feel great though. Cant believe my mood is so much lighter. Still feeling exhausted though

006 09.xx.xx The tiredness is really getting me down now. I feel like I just cant lift it. I am getting enough sleep but still feel tired.

006 10.xx.xx Feel like I cant be bothered about anything. 001 10.xx.xx Fatigue, fuzzy-headed, sore muscles, slight h/a.

Very tired, sleepy. Fell asleep in front of TV.

001 14.xx.xx Very tired. Sleepy this evening. IRRITABILITY: 004 00.08.47 Feel spaced out, head feels as though I have a hangover or have not had

enough sleep. Am agitated, on edge, easily irritated by sudden loud noises. 004 02.05.xx Arrive at swimming pool and am immediately irritated by people in my

group (am usually friendly and outgoing), people are helpful, but I want to be left alone, I dont want to communicate. Lights and noise make me feel high, out of it. Can only concentrate on one task at a time, find myself explaining that I am proving a remedy and feel like I have had lots of M.S.G. Body feels as though swimming, < in swimming pool and headache begins to lift. (Feel normal at 1pm)

001 05.10.xx Feel extremely irritable - research at Record Office has to be repeated because what I did last is unreliable. Arrive home wanting to relax but have to prepare dinner etc. Both partner and son seem incredibly unhelpful and slow

001 06.09.xx Irritable - felt as if I had to do all the work and family sat around doing nothing. Although in fact both children helped with dinner.

007 06.xx.xx She has felt better in herself - less irritable and not so argumentative (curative)

001 07.09.xx Feel tired; quiet day at work makes it more tiring. Tired and irritable with family especially around dinner-cooking time - usual stuff, "I'm doing all the work whilst rest of family are relaxing, etc."

001 13.xx.xx Felt more assertive today at college - couldn't be bothered with some niggly stuff that came up re "group dynamics" - just went and got it sorted out with the people concerned; being straight, direct with them but also seeing funny side of things

001 42.xx.xx Woke feeling very irritable, very depressed, and very snappy with partner and son. Tired; lack of energy. Cross with self and others. Continued to feel very depressed, really awful, like severe PMT, full of negativity. Very irritable with partner when he phoned at lunchtime. By late afternoon, developed severe headache - as this got worse, my mood lifted and by 5.30pm headache was terrible, but felt much better in myself. Felt as if this was the poison finally coming out.

LAUGH/LIVELY/HIGH: 004 00.13.57 Feeling giggly and not quite together 001 01.12.xx Feel relaxed, but lively - have had a lot of laughs today and this evening. 004 02.05.xx Lights and noise make me feel high, out of it. Can only concentrate on one

task at a time, find myself explaining that I am proving a remedy and feel like I have had lots of M.S.G.

003 03.03.xx Decide to go out for a bike ride. Very unusual for me, as I usually sit at home feeling stressed about not getting my college work done when Im not at work. Ride by the rough sea and feel really exhilarated.

001 03.05.xx Had lots of laughs with work colleagues. 006 03.xx.xx I do feel lighter in my mood and generally less grumpy 001 04.09.xx Felt calm and happy. 003 04.xx.xx Feel like going for a short walk after dropping child off at school wouldnt

usually do this. Feel the need for exercise, but also enjoy the sensation of doing something different.

006 04.xx.xx Feel my mood has improved, lighter. Usually quite moody and grumpy. 006 06.xx.xx Mood is still lighter. Dont feel so grim. 006 07.xx.xx Mood is still light and feel so much more laid back 006 08.xx.xx Not being very productive at work, but not worried about it.

Feel great though. Cant believe my mood is so much lighter. Still feeling exhausted though

003 11.xx.xx I have noticed that I am more talkative than usual I have the sensation that

I am gabbling, and that other people cant get a word in edgeways. 004 12.xx.xx At college and finding it hard to be in the group, am tuning out and feeling

silly and giggly. 001 13.xx.xx Felt more assertive today at college - couldn't be bothered with some niggly

stuff that came up re "group dynamics" - just went and got it sorted out with the people concerned; being straight, direct with them but also seeing funny side of things

001 xx.xx.xx Also I dreamt my partner and I were both having diarrhoea - doing it at the same time, together. I had to go and have a shower after, as it was so messy! This was just normal/OK in the dream, not disgusting at all. Made me laugh when I woke up. (I do not often remember my dreams, so it was unusual for me to recall dreaming this much)

PROBLEMS WITH FOOD: 001 05.06.xx I realise I have eaten more chocolate than usual the last few days- have had

wind/heartburn all day today - probably because of this. 001 08.xx.xx Feel as if have been eating far too much sugar/bread - all stuff that gives me

bloating. Have been very bad the last week and need to get a grip! No more chocolate! Feel tired, low, negative. (Still eating foods which disagree - this time, it's crumpets)

001 13.xx.xx Have decided to go on renewed healthy eating regime from tomorrow. Im getting fed up with constant bloating, wind, indigestion together with inability to stop eating foods which aggravate it

001 14.xx.xx From now on I was craving all the foods that gave me indigestion and I couldn't understand why. I felt increasingly upset/depressed/cross with myself - why was I eating all this rubbish all the time again? I gained weight, and my energy was generally low. I was tempted several times to take another of the proving remedy - I wanted that calm, alert, happy feeling again.

001 38.xx.xx Feeling quite depressed, negative for no apparent reason, missing my mother (who died in '97), feeling generally cheesed off with myself and with life. Couldn't understand why I felt like that. Particularly fed-up with my eating habits and feeling bloated and full of wind all the time. An element of self-disgust to this.

001 42.xx.xx Head felt muzzy, slight nausea. Feel as if full of poison - coming out of my mouth when I spoke, in the food I have been eating. Ate nothing till lunchtime and felt strong aversion to sugar/sweet foods. Continued to feel very depressed, really awful, like severe PMT, full of negativity. Very irritable with partner when he phoned at lunchtime. By late afternoon, developed severe h/a - as h/a got worse, mood lifted and by 5.30pm h/a was terrible, but felt much better in myself. Felt as if this was the poison finally coming out.

004 Comment Have gained about 3lbs since starting the proving DEAD/GRIEF: 003 00.10.00 Dream: Close friend calls me to tell me her two daughters have died in the

night from a mild fever. I feel grief stricken and disbelieving. A couple of days later I watch through my window as the bodies are taken away in a flurry of people. They are not in coffins but being carried upright as if they are alive. I see that the youngest girls eyes are open it is as if she looks at me, but I can see that she is dead. The reality in the dream is very sinister I can see their blonde hair blowing in the breeze. I have t0 tell my own daughter that her friends are dead, and feel guilty that I can do nothing to help. Wake up crying.

003 31.XX.XX Dream: A friend with daughter same age as mine told me she had a son aged three who died after she lost him in a shopping centre. Feel shock

that she never told me before; it seems very strange that I didnt know this. Like the dream on day 0, wake up feeling confused about the reality of the situation.

001 38.xx.xx Feeling quite depressed, negative for no apparent reason, missing my mother (who died in '97), feeling generally cheesed off with myself and with life. Couldn't understand why I felt like that.

VERTIGO

005 00.00.45 Felt a little shaky & light-headed, like had been spun around, > bending down.

007 00.06.15 Had some vertigo - spatial awareness changed. The floor didnt feel as though it was where it should be. Maybe not really focusing. It wasnt a fainting feeling. It only happened when she was walking around, not when she was sitting or standing

005 01.10.xx Still feeling light-headed today, but when dancing around to music and shaking my head, felt giddy.

004 02:14.xx Bent forward and felt very dizzy 004 03:17.xx Shopping, bent over trolley and felt dizzy in my body, then legs and head,

lasted for a few minutes. 005 04.07.xx Feeling spaced-out and giddy and my head feels like it is full of warm liquid if

I move my head quickly. 09.06.xx Felt giddy and light-headed again with some nausea HEAD

00x 01.06.xx Occasional waves of dizziness fleet across my head 006 01.27.xx Feel fuzzy headed 006 02.xx.xx Fuzzy feeling in head, cloudy feeling. 006 07.xx.xx Head feels full, heavy, like a bubble with the world going on around it. 006 11.xx.xx Short, sharp headache above eyeballs, stabbing in and out sensation. HEAD PAIN

00x 00:08:47 Aware that I have been having headaches all day. They vary from oppressive to a dull stamp through back of eye and head. Mostly right sided and pressure on top of head

001 01.00.xx Woke with headache; slightly nauseous. 001 01.02.xx Still got headache with slight nausea. Feeling as if bruised ache all over

head. 001 01.03.xx On bus to work headache became quite bad.

shading eyes. Not better for rubbing/pressure - which my headaches usually are. Sensation of a line from top of head above left eye, going right down through head - sore bruised feeling along that line. With aching and sense of pressure in ears & left cheek. > walking in fresh air. The intense line of pain lasted about 1 hour. Awareness of h/a in background for further 3 hours.

004 01:03xx Yesterdays headache is back; left sided, pressure beneath left eye through to middle of nose

004 01:07XX Sensation of pressure through right sinus, under right eye and at bottom of neck pushing down to muscle joining clavicle, sensation comes and goes.

007 01.xx.15 Dull headache, started at the back of her head then moved to top right behind her eye. Occasionally changes to a sudden intense pain lasting for a few seconds only

007 01.xx.38 Headache got really bad. Her whole head felt as if it was going to burst. She hadnt had time to eat. She went to bed and went straight to sleep. She had been physically tired all day and she just wanted to sleep. Felt

despondent - like she couldnt be bothered. 007 02.xx.xx Slight headache this morning - around mid-morning. It went off a bit after

lunch. Tiredness better today. 004 03:13.xx Return of headache, feel heavy above my eyes, pressure in left sinus below

eyes, pushing inwards feeling. 007 03.xx.xx Headache all day. Dull ache in occiput - but occasionally spreading to top of

head (NS) 004 05:09 I am a passenger in car, and headache starts, pinching sensation at the back

of my head just above my neck. Dull ache in left sinus below left eye. Am aware of feeling spaced out and giggly.

006 11.xx.xx Short, sharp headache above eyeballs, stabbing in and out sensation. 001 12.10.xx After college discussion of proving symptoms, I have come home and

experienced the rod-like h/a pain above left eye - similar to what was discussed, and that I had on day 1. Lasted about 15 minutes.

004 13.xx.xx Block of pain, like a bar across back of head, from ear to ear, squeezing and very painful.

004 15.xx.xx 17.00 sudden heavy headache, feels like a weight behind my eyes and see mind.

003 30.xx.xx Bad headache over right side of head and face, which throbs if I bend forwards. Cheekbones and bones around eye-socket and temple feel like they are being squeezed in a vice. This is in the same area as the neuralgia that I often get, but feels different and much more painful. > putting cool hand over my cheek.

003 32.xx.xx Headache still the same. Have noticed that it gets worse as the day goes on. Have noticed confusion with the headache; dont realise when people are speaking to me. Relieved slightly by having a hot bath and going to bed at 9pm.

37.xx.xx Bending over bath to wash my hair have sudden sharp pain in back of neck on the right hand side. Headache starts to abate after this (trapped nerve?)

001

42.xx.xx Severe h/a, terrible cracking pain all over head. Felt as if this was poison coming out.

EYES

00x 01.06.xx Occasional waves of dizziness fleet across my eyes 006 03.xx.xx Eyes feel cloudy, mucussy, like a thin film over my eyes but vision not

impaired. Black rings under my eyes

006 04.xx.xx Eyes, feel cloudy, but vision fine. Other people notice my eyes look, glassy, and glazed.

001 04.xx.xx Itchy left eye - woke up with it. Want to rub vigorously, which makes it worse. Sensation as of hair in inner corner. Have had this symptom before, but usually when tired - do not usually wake up with it. Itchiness gone by evening but then slightly sore,

EAR

003 01.12.45 Right ear feels very hot and is rather red it feels as if I have banged it. I notice this when I am lying down.

001 02.xx.xx. Ears very itchy right inside, plus feeling as if ears popping. Usual for me to get these itchy ears, but this was v. marked, more than normal.

NOSE

005

00.01.45 Seem acutely aware of things, seem to notice smells more.

FACE

001 00.00.10 Fleeting sharp, stinging pain in left upper cheek in small spot under eye, followed by sensation of warmth: pleasant feeling.

005 01.23.xx Very itchy spots around hairline in front of right ear, like heat spots. 004 02:03.xx Return of dull pressure behind left eye & in sinus below. 004 02:12.xx Fleeting pressure either in sinus below left eye, or across either eyebrow,

on and off throughout the evening 001 004.xx.xx Feel as if sinus ache in eye/cheek area - not bad, just awareness of area - as

if been pushed in face. 001 08.xx.xx Spot has come up on right side of face, an inch above outer corner of

mouth. (I don't get spots all that often) 005 08.00.XX Have noticed while driving to work for the last week that skin on face feels

very dry & tight. Has got progressively worse. 005 09.02.XX Dry skin feeling on face again today on way to work. 004 20.xx.xx Sudden, sharp boring pain through right sinus under the eye. Pain lasted all

day, relieved by climbing on a climbing frame. Pain extended to right shoulder.

003 30.XX.XX Right side of face cheekbone, eye painful and throbbing (with headache) Bones in cheek and temple feel like they are being squeezed in a vice. Better for laying cool hand over cheek, but worse for pressure.

MOUTH

007 00:00:00 Took first dose. Tasted really horrible - a bit like alcohol - metallic 007 00:00:05 Increase of saliva in the mouth 004 01.01.xx Mouth feels moist, but tongue and roof of mouth feel dry and I am thirsty. 004 01.14.xx Have just realised that I have finished off everyones drinks at meal times, I

need sweetened cool liquid 005 00.01.15 Tongue feels fluffy & spongy. 005 01.23.xx Cleaned teeth and noticed that tongue was clean, whereas I usually always

have to brush it. 007 00:02:30 Little bit of pain in the jaw-line. Sometimes happens in cold weather - feels

like a to